Efficacy and safety of long-term use of the drug Diane-35 for the treatment of androgenization symptoms

Composition of Diane-35

Diane-35 tablets contain the active components cyproterone acetate and ethinyl estradiol , as well as a number of additional components: lactose monohydrate, povidone , corn starch, magnesium stearate, magnesium hydrosilicate.
The tablet shell consists of povidone 700,000, sucrose, macrogol 6000 , calcium carbonate , magnesium hydrosilicate, glycerol, titanium dioxide, mountain glycol wax, iron oxide.

Diane-35 tablets po 2mg/0.035mg No. 21x1

Name

Diana-35 table No. 21

Storage conditions

The drug should be stored at room temperature.

Expiration date from date of manufacture

5 years

Product description

Dragee

pharmachologic effect

A combined low-dose monophasic oral contraceptive with an antiandrogenic effect, containing estrogen - ethinyl estradiol and an antiandrogen with gestagenic activity - cyproterone acetate. Cyproterone acetate contained in Diana-35 inhibits the influence of androgens, which are also produced in the female body. Thus, it becomes possible to treat diseases caused by increased production of androgens or specific sensitivity to these hormones. While taking Diane-35, the increased activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea, decreases. After 3-4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive oiliness in hair and skin disappears even earlier. Hair loss, which often accompanies seborrhea, is also reduced. Therapy with Diane-35 in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism; however, the effect of treatment should be expected only after several months of use. Along with the above-described antiandrogenic effect of cyproterone acetate, it also has a pronounced gestagenic effect. The contraceptive effect of Diane-35 is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in the secretion of cervical mucus. The cycle becomes more regular, painful menstruation is less frequent, the intensity of bleeding decreases, resulting in a reduced risk of iron deficiency anemia.

Pharmacokinetics

Cyproterone acetate Absorption After taking Diane-35, cyproterone acetate is completely absorbed from the gastrointestinal tract. Bioavailability - 88%. After oral administration of 1 tablet Diane-35, Cmax is reached after 1.6 hours and is 15 ng/ml. Distribution Cyproterone acetate is almost completely bound to plasma albumin, approximately 3.5-4.0% is in the free state. Since protein binding is nonspecific, changes in sex steroid binding globulin (SGBS) levels do not affect the pharmacokinetics of cyproterone acetate. Up to 0.2% of the dose of cyproterone acetate is excreted in breast milk. Metabolism and excretion The pharmacokinetics of cyproterone acetate is biphasic, T1/2 is 0.8 hours and 2.3 days, respectively, for the first and second phases. Total plasma clearance is 3.6 ml/min/kg. Biotransformed by hydroxylation and conjugation, the main metabolite is a 15?-hydroxyl derivative. It is excreted mainly in the form of metabolites in urine and bile in a ratio of 1:2, a small part is excreted unchanged in bile. T1/2 for cyproterone acetate metabolites is 1.8 days. Ethinyl estradiol Absorption After taking Diane-35, ethinyl estradiol is quickly and completely absorbed from the gastrointestinal tract. During absorption and “first pass” through the liver, ethinyl estradiol undergoes intensive metabolism, which causes a bioavailability of approximately 45% and its significant individual variability. After oral administration of 1 tablet Diane-35, Cmax is approximately 80 pg/ml and is achieved after 1.7 hours. Distribution: Binding to proteins (albumin) in blood plasma is high (2% is found in free form in plasma). Vd is approximately 5 l/kg. Up to 0.02% of the dose of ethinyl estradiol is excreted in breast milk. Ethinyl estradiol increases the hepatic synthesis of SHBG and CSG (corticosteroid binding globulin) during continuous use. During treatment with Diane-35, the serum SHG concentration increases from approximately 100 nmol/l to 300 nmol/l and the serum concentration of DSG increases from approximately 50 μg/ml to 95 μg/ml. Metabolism and elimination The pharmacokinetics of ethinyl estradiol is biphasic, with T1/2 1-2 hours (?-phase) and approximately 20 hours (?-phase), respectively. Plasma clearance is about 5 ml/min/kg. Ethinyl estradiol is excreted from the body in the form of metabolites; about 40% - with urine, 60% - with bile.

Indications for use

Contraception in women with androgenization phenomena; androgen-dependent diseases in women: acne (especially its severe forms, accompanied by seborrhea, inflammatory phenomena with the formation of nodes / papular-pustular acne, nodular cystic acne /), androgenic alopecia and mild forms of hirsutism.

Use during pregnancy and lactation

Diane-35 is contraindicated for use during pregnancy and lactation.

special instructions

Before starting to use Diane-35, it is necessary to conduct a general medical examination (including mammary glands and cytological examination of cervical mucus), exclude pregnancy and disorders of the blood coagulation system. With long-term use of the drug, preventive control examinations must be carried out every 6 months. If there are risk factors, the potential risks and expected benefits of therapy should be carefully assessed and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, worsen, or appear for the first time, discontinuation of the drug may be necessary. The estimated incidence of venous thromboembolism (VTE) when taking low-dose estrogen oral contraceptives (less than 50 mcg ethinyl estradiol) is up to 4 per 10,000 women per year, compared with 0.5-3 per 10,000 women not taking oral contraceptives. However, the incidence of VTE when taking combined oral contraceptives is lower than the incidence of VTE associated with pregnancy (6 per 10,000 pregnant women per year). The patient should be warned that if symptoms of venous or arterial thrombosis develop, she should immediately consult a doctor. These symptoms include unilateral leg pain and/or swelling; sudden severe chest pain radiating to the left arm or without radiating; sudden shortness of breath; sudden attack of coughing; any unusual, severe, prolonged headache; increased frequency and severity of migraines; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; dizziness; collapse with/without partial seizure; weakness or very significant loss of sensation that suddenly appears on one side or in one part of the body; movement disorders; symptom complex “acute” abdomen. The relationship between taking combined oral contraceptives and arterial hypertension has not been established. If persistent arterial hypertension occurs, Diana-35 should be discontinued and appropriate antihypertensive therapy prescribed. Taking the contraceptive can be continued if blood pressure normalizes. If liver dysfunction occurs, temporary discontinuation of Diane-35 may be required until laboratory parameters normalize. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives. Although combined oral contraceptives have an effect on tissue resistance to insulin and glucose tolerance, there is usually no need to adjust the dose of glucose-lowering drugs in patients with diabetes. Nevertheless, this category of patients should be under close medical supervision. Women prone to chloasma should avoid prolonged exposure to the sun and ultraviolet radiation while taking combined oral contraceptives. If symptoms have recently developed or become significantly worse in women with hirsutism, other causes, such as androgen-producing tumor, congenital adrenal dysfunction, should be considered in the differential diagnosis. While taking Diane-35, irregular bleeding (spotting or breakthrough bleeding) may sometimes occur, especially during the first months of therapy. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately 3 cycles. If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures taken to exclude malignancy or pregnancy. These may include diagnostic curettage. In some cases, withdrawal bleeding may not develop during a break in taking the pill. If you do not take the pill regularly or if there are no two menstrual-like bleedings in a row, pregnancy should be excluded before continuing to take the drug.

With caution (Precautions)

If liver dysfunction occurs, temporary discontinuation of Diane-35 may be required until laboratory parameters normalize. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Contraindications

Thrombosis and thromboembolism, incl. history (deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders); conditions preceding thrombosis (including transient ischemic attacks, angina pectoris); diabetes mellitus complicated by microangiopathies; the presence of severe or multiple risk factors for venous or arterial thrombosis; diseases or severe liver dysfunction; liver tumors (including history); hormone-dependent malignant tumors, incl. tumors of the breast or genital organs (including in history); uterine bleeding of unknown etiology; pancreatitis (including a history), if it was accompanied by severe hypertriglyceridemia; a history of migraine, which was accompanied by focal neurological symptoms; lactation (breastfeeding); pregnancy or suspicion of it; hypersensitivity to the components of the drug. If any of these conditions develop for the first time while taking Diane-35, the drug should be discontinued immediately.

Directions for use and doses

Diane-35 is taken orally, 1 tablet/day. The pills are taken without chewing and washed down with a small amount of liquid. The time of taking the drug does not matter, however, subsequent doses should be taken at the same selected hour, preferably after breakfast or dinner. Reception of Diane-35 begins on the 1st day of the cycle, using tablets of the corresponding day of the week from the calendar package. Daily administration of the drug is carried out using tablets from the calendar package sequentially in the direction of the arrow marked on the foil until all tablets have been taken. After finishing taking all 21 tablets from the calendar pack, there is a break in taking the drug for 7 days, during which menstrual-like bleeding occurs. After 28 days from the start of taking the drug (21 days on and 7 days off), i.e. on the same day of the week as at the beginning of the course, continue taking the drug from the next package. When switching from combined oral contraceptives, taking Diane-35 should begin the day after taking the last tablet with the active components of the previous drug, but in no case later than the next day after the usual 7-day break in taking (for drugs containing 21 tablets) . Continue according to the scheme described above. If the patient took the previous contraceptive daily for 28 days, Diane-35 should be started after taking the last inactive pill. When switching from contraceptives containing only gestagens (“mini-pills”), Diane-35 can be used without interruption. When using injectable forms of contraceptives, Diane-35 begins to be taken from the day when the next injection is due. When switching from an implant - on the day of its removal. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. After an abortion in the first trimester of pregnancy, a woman can start taking the drug immediately. In this case, the woman does not need additional methods of contraception. After childbirth or abortion in the second trimester of pregnancy, taking the drug should begin on the 21-28th day. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. If a woman was sexually active in the period between childbirth or abortion and the start of taking Diane-35, then pregnancy should first be excluded or you must wait until the first menstruation. A woman should take the missed pill as soon as possible, and the next pill should be taken at the usual time. If the delay is less than 12 hours, the reliability of contraception does not decrease. If the delay in taking the pill is more than 12 hours, the reliability of contraception may be reduced. It should be borne in mind that the administration of the tablet should never be interrupted for more than 7 days, and that 7 days of continuous administration of the tablet are required to achieve adequate suppression of the function of the hypothalamic-pituitary-ovarian system. If the delay in taking the pill was more than 12 hours (the interval from the moment of taking the last pill is more than 36 hours) during the first and second weeks of taking the drug, then the woman should take the last missed pill as soon as possible, as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. If the delay in taking the pill is more than 12 hours (the interval since taking the last pill is more than 36 hours) during the third week of taking the drug, then the woman should take the last missed pill as soon as possible, as soon as she remembers (even if this means taking two pills at the same time ). The next pill is taken at the usual time. In addition, taking pills from a new package should be started as soon as the current package is finished, i.e. nonstop. Most likely, the woman will not experience withdrawal bleeding until the end of the second pack, but she may experience spotting or breakthrough uterine bleeding on the days she takes the pill. If a woman has vomited within 3 to 4 hours after taking Diane-35, absorption of the active substances may be incomplete. In this case, you need to follow the recommendations when skipping pills. In order to delay the onset of menstruation, a woman should continue taking pills from the new Diane-35 package immediately after taking all the pills from the previous one, without interruption. The pills from this new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking Diane-35 from a new package after the usual 7-day break. In order to postpone the start of menstruation to another day of the week, a woman should shorten the next break in taking the pills by as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and will continue to have spotting and breakthrough bleeding while taking the second package (the same as in the case when she would like to delay the onset of menstruation). When treating hyperandrogenic conditions, the duration of use is determined by the severity of the disease. After the symptoms disappear, it is recommended to take Diane-35 for at least another 3-4 months. If a relapse occurs several weeks or months after completion of the course, Diane-35 can be re-treated.

Overdose

Symptoms: nausea, vomiting, slight vaginal bleeding (in girls). Treatment: carry out symptomatic therapy. There is no specific antidote.

Side effect

From the endocrine system: in rare cases - engorgement, soreness, enlargement of the mammary glands and discharge from them, change in body weight. From the reproductive system: in rare cases - intermenstrual bleeding, changes in vaginal secretion, changes in libido. From the side of the central nervous system: in rare cases - headache, migraine, decreased mood. From the digestive system: in rare cases - nausea, vomiting. Other: in very rare cases - poor tolerance to contact lenses, allergic reactions, the appearance of age spots on the face (chloasma). The listed side effects may develop in the first few months of taking Diane-35 and usually decrease over time.

Compound

Active substance: ethinyl estradiol 35 mcg; cyproterone acetate 2 mg; Excipients: lactose monohydrate - 31.115 mg, corn starch - 18 mg, povidone - 2.1 mg, talc (magnesium hydrosilicate) - 1.65 mg, magnesium stearate - 0.1 mg. Shell composition: sucrose - 19.371 mg, povidone 700,000 - 0.189 mg, macrogol 6000 - 2.148 mg, calcium carbonate - 8.606 mg, talc (magnesium hydrosilicate) - 4.198 mg, titanium dioxide - 0.274 mg, glycerol - 0.137 mg, mountain glycol wax - 0.05 mg, iron (II) oxide - 0.027 mg.

Interaction with other drugs

With simultaneous use of Diane-35 with inducers of microsomal liver enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin; and also, possibly, with oxcarbazepine, topiramate, felbamate and griseofulvin), the clearance of ethinyl estradiol and cyproterone increases, which can lead to breakthrough uterine bleeding or decreased reliability of contraception. When used simultaneously with ampicillins and tetracyclines, the contraceptive reliability of Diane-35 is reduced.

Release form

Dragee 1 dragee Active substance: ethinyl estradiol 35 mcg; cyproterone acetate 2 mg; Excipients: lactose monohydrate - 31.115 mg, corn starch - 18 mg, povidone - 2.1 mg, talc (magnesium hydrosilicate) - 1.65 mg, magnesium stearate - 0.1 mg. Shell composition: sucrose - 19.371 mg, povidone 700,000 - 0.189 mg, macrogol 6000 - 2.148 mg, calcium carbonate - 8.606 mg, talc (magnesium hydrosilicate) - 4.198 mg, titanium dioxide - 0.274 mg, glycerol - 0.137 mg, mountain glycol wax - 0.05 mg, iron (II) oxide - 0.027 mg. 21 pcs. - blisters (1) - cardboard packs.

pharmachologic effect

Diane-35 is a monophasic combined oral contraceptive that has antiandrogenic, estrogenic, contraceptive, and gestagenic effects. This is a combination product that contains estrogen - ethinyl estradiol, as well as the antiandrogen substance cyproterone acetate, which demonstrates gestagenic properties.

Under the influence of the drug, the increased viscosity of the cervical mucus remains, which makes it difficult for sperm to enter the uterine cavity. As a result, a contraceptive effect is noted. The substance cyproterone acetate blocks androgen receptors and reduces the phenomenon of androgenization in women, reducing the severity of sebum production, hair loss, and the growth of unwanted hair. Also provides treatment for diseases associated with excess production of androgens or high sensitivity to them.

In the process of taking Diane-35 in women, the severity of acne , and the number of new acne decreases. The substance also exhibits gestagenic activity, inhibiting the ovulation process.

The contraceptive effect of the drug is observed by the 14th day from the start of its use and remains during a seven-day pause in use. When using a contraceptive, the menstrual cycle is normalized, menstruation becomes less painful, the intensity of bleeding decreases and, as a result, the likelihood of iron deficiency anemia .

Pharmacological properties of the drug Diane-35

Both active ingredients included in the drug Diane-35 have a positive effect on the state of hyperandrogenism. Cyproterone acetate is a competitive antagonist of androgen receptors; it inhibits the synthesis of androgens and determines a decrease in the concentration of these hormones in the blood due to an antigonadotropic effect. This antigonadotropic effect is enhanced by ethinyl estradiol, which also regulates the synthesis of sex steroid binding globulin (SHBG) in the blood plasma. Taking this into account, the level of unbound biologically available androgen in the blood decreases. When using the drug Diane-35 (usually after 4 months of therapy), acne is eliminated, excessive oily hair and skin disappears even earlier. Hair loss, which often accompanies seborrhea, is also reduced. When using the drug by persons with mild forms of hirsutism (primarily with mild facial hair), the results of therapy should be expected only after several months from its start. The contraceptive effect of the drug Diane-35 is based on the interaction of various factors, the most important of which are suppression of ovulation and changes in cervical secretion. In addition to preventing pregnancy, the drug has a number of positive properties. The menstrual cycle becomes more regular, menstruation is less painful, and blood loss decreases. The latter helps reduce the incidence of iron deficiency anemia. The toxicity profile of ethinyl estradiol has been well studied. There are no preclinical data to supplement the information regarding the safety of ethinyl estradiol indicated in the sections of the instructions for medical use of the drug. Data from standard preclinical toxicity studies following repeated use of cyproterone acetate do not indicate the existence of any specific risk to the human body. Available clinical experience does not suggest an increased incidence of liver tumors in humans. Carcinogenicity studies of cyproterone acetate in rodents do not indicate the existence of any specific carcinogenic effect. However, it should be taken into account that sex steroids may promote the growth of certain pre-existing hormone-dependent tumors. Available data provide no basis to oppose the use of Diane-35 in humans when taken in accordance with the instructions provided and at the recommended dose. Cyproterone acetate After oral administration, cyproterone acetate is rapidly and completely absorbed. Its peak serum concentration is 15 ng/ml and is achieved approximately 1.6 hours after a single dose. The bioavailability of cyproterone acetate is approximately 88%. Cyproterone acetate is almost completely bound to albumin in the blood serum. Only 3.5–4% of the total steroid concentration remains in an unbound state. Ethinyl estradiol-induced increase in SHPS levels does not affect protein binding of cyproterone acetate. Cyproterone acetate is almost completely metabolized. The main metabolite in blood plasma is 15b-OH-CPA. The clearance rate from serum is approximately 3.6 ml/min/kg. The serum concentration of cyproterone acetate decreases biphasically, with half-lives of 0.8 hours and 2.3–3.3 days. Some of the steroid is excreted unchanged. Metabolites are excreted in urine and bile in a 1:2 ratio. The half-life of metabolites is 1.8 days. Taking into account the long half-life of cyproterone acetate from blood serum, its accumulation in the blood serum can be observed during one cycle of therapy with a coefficient of 2–2.5. Ethinyl estradiol Adsorption When taken orally, ethinyl estradiol is rapidly and completely absorbed. A peak serum concentration of approximately 71 pg/mL is achieved after 1.6 hours. Distribution Ethinyl estradiol binds strongly, but not specifically, to serum albumin (approximately 98%) and induces an increase in serum GSPC concentrations. Ethinyl estradiol is metabolized mainly by aromatic hydroxylation, resulting in a large number of hydroxylated and methylated metabolites, among which there are both free metabolites and conjugates with glucuronides and sulfates. Clearance is 2.3–7 ml/min/kg. Serum ethinyl estradiol levels decrease in 2 phases with half-lives of approximately 1 and 10–20 hours, respectively. The substance is not excreted from the body unchanged; ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 4:6. The half-life of metabolites is approximately 1 day. Equilibrium concentration is achieved in the second half of the administration cycle, when the level of the active substance in the blood serum is 60% higher compared to a single dose.

Pharmacokinetics and pharmacodynamics

The highest concentration of cyproterone acetate is observed 1.6 hours after taking the pills. Its bioavailability is 88%. In the first and second phases of elimination, the half-life of the substance cyproterone acetate is 3-4 hours and 2 days.

Ethinyl estradiol is rapidly absorbed after oral administration, the highest concentration in the blood is observed after 1.6 hours. The bioavailability of the substance is 45%. Almost completely nonspecifically binds to albumin. The half-life of the substance ethinyl estradiol occurs in two phases - 1-3 hours and 1 day.

In breast milk, approximately 0.2% of the dose of cyproterone acetate and approximately 0.02% of ethinyl estradiol are determined.

Buy Diane-35 film-coated tablets No. 21 in pharmacies

Instructions for use Diane-35

Buy Diana-35 dr

Dosage forms of dragees Manufacturers Bayer Weimar GmbH and Co. KG, packaged Bayer Pharma AG (Germany), Schering AG (Germany) Group Various combined estrogen-gestagen-antiandrogen agents Composition Active substances: 2 mg of cyproterone acetate and 0.035 mg of ethinyl estradiol. International nonproprietary name Ethinyl estradiol + Cyproterone Synonyms Bellune 35, Chloe, Erica-35 Pharmacological action Estrogenic, antiandrogenic, progestogenic, contraceptive. Cyproterone acetate competitively blocks tissue androgen receptors, lowers the level of androgens in the blood, reduces (eliminates) androgenization phenomena (seborrhea, androgenetic alopecia, hirsutism, acne) in women due to inhibition of intracellular processes mediated by hormone receptor complexes, has gestagenic activity; in combination with ethinyl estradiol, it inhibits the secretion of gonadotropic hormones by the pituitary gland and inhibits ovulation, increases the viscosity of cervical mucus, which makes it difficult for sperm to enter the uterine cavity (contraceptive effect). In addition, the endometrium remains unprepared for implantation. In addition to preventing pregnancy, the combination of estrogen and cyproterone acetate has antiandrogenic effects, which may be useful when choosing a method of birth control in women with androgenization. Normalizes the menstrual cycle, painful menstruation is less common, the intensity of bleeding decreases, resulting in a reduced risk of iron deficiency anemia. Indications for use Androgen-dependent hyperandrogenic diseases in women: acne (especially forms accompanied by seborrhea, inflammation and nodule formation), alopecia, hirsutism, contraception in women, incl. suffering from these diseases. Contraindications Hypersensitivity to the components of the drug, pregnancy, breastfeeding, severe liver dysfunction, liver tumors and thromboembolic processes (including a history), diabetes mellitus with vascular complications, hormone-dependent breast and endometrial cancer, vaginal bleeding of unknown etiology. Side effect: Organ of vision. Rarely: intolerance to contact lenses. Gastrointestinal tract. Common: nausea, abdominal pain; uncommon: vomiting, diarrhea. The immune system. Rarely: hypersensitivity reactions. General symptoms. Often: weight gain; rarely: weight loss. Metabolism. Uncommon: fluid retention. Nervous system. Often: headache; uncommon: migraine. Psychiatric disorders. Common: decreased mood, mood swings; uncommon: decreased libido; rarely: increased libido. Reproductive system and mammary glands. Often: pain in the mammary glands, engorgement of the mammary glands; uncommon: breast hypertrophy; rarely: vaginal discharge, breast discharge. Skin and subcutaneous tissues. Uncommon: rash, urticaria; rarely: erythema nodosum, erythema multiforme. The following serious adverse events have been reported in women using combined oral contraceptives. Venous thromboembolic disorders. Arterial thromboembolic disorders. Stroke. Hypertension. Hypertriglyceridemia. Changes in glucose tolerance or effects on peripheral insulin resistance. Liver tumors (benign and malignant). Impaired liver function parameters. Chloasma. In women with hereditary angioedema, exogenous estrogens may cause or worsen symptoms of angioedema. The onset or worsening of conditions for which the connection with the use of combined oral contraceptives is not indisputable: jaundice and/or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis; Crohn's disease; ulcerative colitis; cervical cancer smears. The incidence of breast cancer diagnosis in women using oral contraceptives is increased only slightly. Breast cancer is rarely observed in women under 40 years of age, the excess incidence is insignificant in relation to the overall risk of breast cancer. The cause-and-effect relationship between the occurrence of breast cancer and the use of COCs has not been established. Interaction Interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and/or decreased contraceptive effectiveness. Women taking these drugs should temporarily use barrier methods of contraception in addition to the drug, or choose another method of contraception. Effect on hepatic metabolism: the use of drugs that induce liver microsomal enzymes can lead to an increase in the clearance of sex hormones. Such drugs include: phenytoin, barbiturates, primilon, carbamazspin, rifampicin; There are also suggestions for oxcarbazepine, toniramate, felbamate, griseofulvin and preparations containing St. John's wort. HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and combinations thereof also have the potential to affect hepatic metabolism. Effect on enterohepatic circulation: According to individual studies, some antibiotics (for example, penicillins and tetracyclines) may reduce the enterohepatic circulation of estrogens, thereby reducing the concentration of ethinyl estradiol. While taking medications that affect microsomal enzymes, and for 28 days after their discontinuation, you should additionally use a barrier method of contraception. While taking antibiotics (excluding rifampicin and griseofulvin) and for 7 days after their discontinuation, you should additionally use a barrier method of contraception. If the period of use of the barrier method of protection ends later than the pill in the package, you need to move on to the next package without the usual break in taking the pill. Oral combination contraceptives may affect the metabolism of other drugs, resulting in increased (eg cyclosporine) or decreased (eg lamotrigine) plasma and tissue concentrations. Other forms of interaction. The use of drugs such as Diane-35 may affect the results of certain laboratory tests, including biochemical parameters of the liver, plasma protein concentrations (for example, corticosteroid binding globulin, lipid/lipoprotside fractions, parameters of hemostasis and fibrinolysis, carbohydrate metabolism). These changes usually remain within normal physiological values. Method of administration and dosage To achieve a therapeutic effect and ensure the necessary contraception, the drug should be taken regularly. If any other hormonal contraceptive drug was used before starting Diane-35, its use should be discontinued. The dosage regimen of the drug coincides with the dosage regimen of most oral contraceptives. Thus, the rules for taking other oral contraceptives apply to taking Diane-35. Irregular use can lead to intermenstrual bleeding, a decrease in the therapeutic effect and contraceptive effectiveness. When used correctly, the Pearl index is approximately 1. Diane-35 dragee should be taken orally in the order indicated on the package, every day at approximately the same time, with a small amount of water. Take one tablet per day continuously for 21 days. The next package begins after a 7-day break from taking the pills, during which withdrawal bleeding usually occurs. Bleeding usually begins 2-3 days after taking the last pill and may not stop until you start taking a new package. How to start reception. If you have not taken any hormonal contraceptives in the previous month. Taking the drug begins on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding). It is possible to start taking it on days 2-5 of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the pills from the first package. When switching from other combined oral contraceptives, vaginal ring or contraceptive patch. It is preferable to start taking the next day after taking the last hormonal tablet from the previous package, but in no case later than the next day after the usual 7-day break (for preparations containing 21 tablets) or after taking the last inactive tablet (for preparations containing 28 dragee in packaging). Taking the drug should begin on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied. When switching from contraceptives containing only gestagens (mini-pills, injection forms, imilant), or from a gestagen-releasing intrauterine therapeutic system (Mirena). You can switch from the mini-pill to Diana-35 on any day (without a break), from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from the injection form - from the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. After an abortion in the first trimester of pregnancy. A woman can start taking the drug immediately - on the day of the abortion. If this condition is met, the woman does not need additional contraceptive protection. After childbirth or abortion in the second trimester of pregnancy. You should start taking the drug no earlier than 21-28 days after birth in the absence of breastfeeding or after an abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. However, if a woman has already been sexually active, before starting to take the drug it is necessary to exclude pregnancy or wait until her first menstruation. Taking missed pills. If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. A woman should take a pill as soon as possible, and the next one should be taken at the usual time. If the delay in taking the pill is more than 12 hours, contraceptive protection may be reduced. The more tablets you miss, and the closer the missed tablet is to the 7-day break in taking the tablets, the greater the likelihood of pregnancy. In this case, you can be guided by the following two basic rules: Taking the drug should never be interrupted for more than seven days. To achieve adequate suppression of hypothalamic-pituitary-ovarian regulation, 7 days of continuous use of the pill are required. Accordingly, the following advice can be given if the delay in taking the pill is more than 12 hours (the interval from the moment you took the last pill is more than 36 hours): The first week of taking the drug. A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (for example, a condom) should be used for the next 7 days. If sexual intercourse took place within a week before missing the pills, the possibility of pregnancy must be taken into account. Second week of taking the drug A woman should take the last missed tablet as soon as possible, as soon as she remembers (even if this means taking two tablets at the same time). The next pill is taken at the usual time. Provided that the woman took the pill correctly during the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for 7 days. Third week of taking the drug. The risk of pregnancy increases due to the upcoming break in taking the tablets, however, if during the 7 days preceding the first missed tablet all tablets were taken correctly, there is no need to use additional contraceptive methods. 1. A woman should take the last pill she missed as soon as possible, as soon as she remembers (even if this means taking two pills at the same time). The next pills are taken at the usual time, until the pills from the current package run out. The next pack should be started immediately. Withdrawal bleeding is unlikely until the second pack is finished, but spotting and breakthrough bleeding may occur while taking the tablets. 2. A woman can also stop taking pills from the current package. Why should she take a break for 7 days, including the day she missed the pills, and then start taking a new pack. If a woman misses taking pills and then does not have withdrawal bleeding during the break, pregnancy must be ruled out. Recommendations in case of vomiting and diarrhea. In case of vomiting or diarrhea within 4 hours after taking the pills, absorption may not be complete; therefore, additional measures must be taken to protect against unwanted pregnancy. In such cases, you should follow the above recommendations when skipping pills. Changing the day the menstrual cycle begins. In order to delay the onset of menstruation, a woman should continue taking pills from the new Diane-35 package immediately after taking all the pills from the previous one, without interruption. The pills from this new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking the drug from a new pack after the usual 7-day break. In order to postpone the start of menstruation to another day of the week, a woman should be advised to shorten the next break in taking the pills by as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and will continue to have spotting and breakthrough bleeding while taking the second pack (as well as in the case when she would like to delay the onset of menstruation. Duration of use. Duration of taking pills depends on the severity of the symptoms of androgenization and the response to treatment. Basically, treatment is carried out over several months. The response to the treatment of acne and seborrhea usually occurs faster than the response to the treatment of hirsutism or alopecia. It is recommended to take the drug for at least 3-4 courses after the signs of the disease disappear If the disease relapses several weeks or months after stopping the tablets, treatment with the drug may be resumed. If the drug is resumed (after a break of four weeks or more), the increased risk of VTE should be taken into account. Additional information for certain patient groups. Children and adolescents The drug is indicated only after menarche. Elderly patients. Not applicable. The drug is not indicated after menopause. Patients with liver disorders. The drug is contraindicated in women with severe liver disease until liver function tests return to normal. Patients with kidney disorders. The drug has not been specifically studied in patients with renal impairment. Available data do not suggest changes in treatment in these patients. Overdose No data available. Storage conditions List B. At room temperature.

Indications for use

The drug is used to prevent pregnancy in women who exhibit androgenization (that is, the manifestation of male traits provoked by the action of male sex hormones).

The drug is also indicated for manifestations of androgenization : seborrhea, acne, mild forms of alopecia , hirsutism .

Sometimes the medicine is recommended for diseases of the female reproductive system, in particular, polycystic ovary syndrome .

Contraindications

The following indications for the use of the drug Diane-35 are determined:

• period of pregnancy and breastfeeding, suspicion of pregnancy;
• liver damage;
• history of itching or idiopathic jaundice during pregnancy;
• thrombosis and thromboembolism ;
• angina pectoris , transient ischemic attacks;
• Dubin-Johnson and Rotor (hereditary liver diseases);
• and breast cancer
• disorders of fat metabolism;
• history of blistering dermatosis
• otosclerosis , worsening during previous pregnancies;
• diabetes mellitus , accompanied by vascular complications;
• hormone-dependent malignant diseases;
• vaginal bleeding.

Contraindications to the use of the drug Diane-35

COCs should not be used if you have at least one of the following conditions or diseases. If any of these conditions or diseases occur for the first time while using a COC, the drug should be stopped immediately. Venous or arterial thrombotic/thromboembolic events (eg deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular disorders, current or in history. The presence or history of prodromal symptoms of thrombosis (transient cerebrovascular accident, angina pectoris). History of migraine with focal neurological symptoms. Diabetes mellitus with vascular damage. The presence of severe or multiple risk factors for venous or arterial thrombosis may also be a contraindication (see SPECIAL INSTRUCTIONS). Current or history of pancreatitis if associated with severe hypertriglyceridemia. Current or history of severe liver disease until liver function tests return to normal. Liver tumors (benign or malignant) - diagnosed or present in history. Diagnosed or suspected malignant tumors (for example, genitals or mammary glands) that are dependent on sex hormones. Vaginal bleeding of unknown etiology. Diagnosed or suspected pregnancy. Hypersensitivity to the active substances or to any of the components of the drug. The drug Diane-35 is not prescribed to men.

Side effects of Diane-35

During administration, the following side effects of Diane-35 may occur:

• endocrine system: soreness of the mammary glands, the appearance of discharge from them, weight changes;
• reproductive system: the appearance of bleeding between menstruation, changes in libido, changes in vaginal secretion;
• nervous system: migraine , headaches, unstable mood;
• digestive system: vomiting, nausea;
• other manifestations: allergic manifestations, poor tolerance of contact lenses, chloasma.

These side effects rarely develop when taking the drug. As a rule, negative manifestations occur in the first months of taking Diane-35; over time, their severity decreases.

Many women are concerned about the connection between taking Diane-35 and weight gain. As a rule, weight gain when using a contraceptive occurs only in some cases. If such a side effect develops, a woman needs to adjust her diet and lifestyle, and also consult a doctor.

Interactions of the drug Diane-35

Interactions between drugs containing a combination of estrogen/progestagen (such as Diane-35) and other drugs may lead to breakthrough bleeding and/or loss of contraceptive effectiveness. The following interactions have been reported in the literature. Hepatic metabolism: Interactions may occur with drugs that induce microsomal enzymes, which can cause an increase in the clearance of sex hormones (for example, phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and drugs containing St. John's wort). Interaction with the enterohepatic circulation: Some clinical studies suggest that the enterohepatic circulation of estrogens may be decreased by certain antibiotics that reduce ethinyl estradiol concentrations (such as penicillin and tetracycline antibiotics). When treating any of the above drugs, a woman should temporarily use a barrier method in addition to taking Diane-35 or choose another method of contraception. When treating with drugs that induce microsomal enzymes, the barrier method should be used throughout the entire period of treatment with the corresponding drug and for another 28 days after stopping its use. When treating with antibiotics (excluding rifampicin and griseofulvin), the barrier method should be used for another 7 days after discontinuation of the antibiotic. If the barrier method is still being used, and the tablets in the Diane-35 package have already run out, taking the tablets from the next package should be started without the usual break. Oral contraceptives containing estrogen/progestogen (such as Diane-35) may affect the metabolism of other drugs. Therefore, the concentrations of active substances in blood plasma and tissues (for example, cyclosporine) may change. Note. To establish the potential for interaction with drugs that are prescribed concomitantly with Diane-35, it is recommended that you read the instructions for the medical use of these drugs. Impact on laboratory test results Taking contraceptive drugs such as Diane-35 may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, indicators of the content of such proteins (carriers) in the blood plasma, as a globulin that binds sex hormones and lipid/lipoprotein fractions, parameters of carbohydrate metabolism, as well as parameters of coagulation and fibrinolysis.

Diane-35 tablets, instructions for use (Method and dosage)

The provided instructions for use of Diane-35 provide for oral administration of the pill. To ensure the necessary contraception of active substances in the body, you need to take the drug regularly.

If a woman has used any other hormonal contraceptives, stop using Diane-35 before taking it.

The dosage regimen of this contraceptive is the same as that of other oral contraceptives. If you do not take this medication regularly, acyclic bleeding may occur and the therapeutic and contraceptive effect may decrease.

Diana-35 calendar pack contains 21 tablets. For ease of use, each pill is marked with the day of the week on which it should be taken. You need to swallow the pills at the same time, washing down the drug with liquid. You need to take the pills in the direction of the arrow until all the pills have been taken. After completing the dose, you do not need to drink the drug for 7 days. During these days – usually on days 2-3 – withdrawal bleeding begins. After a seven-day break, you need to start the next package, adhering to this regimen, even if the bleeding has not stopped. That is, a woman always starts a new package of Diana-35 on the same day of the week.

You should start taking the pills on the first day of your monthly bleeding. For convenience, you should use the first tablet marked with the day of the week on which you begin taking it. Next, the pills are taken in order.

The contraceptive effect is observed from the first day of administration, therefore, there is no need to use other contraceptives .

You can start drinking Diane-35 on days 2-5 of your cycle. But at the same time, barrier contraception should be used additionally during the first 7 days of admission.

If a woman switches to Diane-35 after using any other methods of contraception, she should additionally consult a gynecologist.

After an early abortion, a woman can start taking pills immediately. In this case, no additional protection is required.

After a miscarriage or spontaneous abortion, you should consult a doctor who will tell you how to take contraceptives.

After a late abortion and childbirth, it is recommended to start taking the pills on days 21-28. If a woman has already had sexual intercourse before starting to take the medicine, it is necessary to initially rule out pregnancy or wait until the first menstruation begins.

If you missed taking the pill, you need to take it as quickly as possible and take the next pill at the usual time. It should be taken into account that if you are less than 12 hours late, the contraceptive effect does not decrease.

The likelihood of conception increases the more pills a woman misses and the closer the skips are to the seven-day break. If you miss taking the drug for many days, you should consult your doctor.

If a woman experiences vomiting or diarrhea within 3-4 hours after taking the pill, it is advisable to use additional contraceptive methods.

When used for treatment, its duration depends on the severity of symptoms. As a rule, taking the medicine lasts several months. When using an anti-acne product, the period of use may be shorter, as evidenced by reviews.

Diane-35 tablets according to No. 21

Compound

Active ingredients: cyproterone acetate - 2 mg, ethinyl estradiol - 0.035 mg. Excipients: lactose monohydrate, corn starch, povidone 25, talc (magnesium hydrosilicate), magnesium stearate.

Pharmacokinetics

Cyproterone

completely absorbed after oral administration. Cmax in blood serum is achieved 1.6 hours after administration in combination with ethinyl estradiol and is 15 ng/ml. Bioavailability - 88%. Almost completely binds to plasma albumin. During the course of treatment, cumulation is observed: serum concentration increases from 15 ng/ml on the 1st day of treatment to 21 ng/ml at the end of the 1st cycle and to 24 ng/ml at the end of the 3rd treatment cycle. AUC increases 2.2 times (end of cycle 1) and 2.4 times (end of cycle 3). The Css is generated approximately 16 days after the start of treatment. Metabolized in the liver through various reactions, incl. hydroxylation and conjugation. The main metabolite is 15-hydroxycyproterone. T1/2 from plasma is biphasic, T1/2 is 0.8 hours and 2.3 days, respectively, for the first and second phases. Total plasma clearance is 3.6 ml/min/kg. The main part of the administered dose is excreted by the kidneys in the form of metabolites, the remaining part is excreted unchanged in bile. T1/2 is 1.9 days.

After oral administration of ethinyl estradiol

quickly and completely absorbed. Cmax in blood serum is reached after 1.7 hours and is 80 pg/ml. Almost completely binds to plasma proteins. During absorption and “first pass” through the liver, it is metabolized, which leads to a decrease in bioavailability. The apparent Vd is 5 l/kg. Css is created 3-4 days after the start of treatment. T1/2 from plasma is biphasic, T1/2 is 1-2 hours and 20 hours, respectively, for the first and second phase. Plasma clearance – 5 ml/min/kg. It is excreted in the form of metabolites through the intestines and kidneys in a ratio of 4:6, T1/2 is about 1 day.

Indications for use

Contraception in women with androgenization phenomena; treatment of androgen-dependent diseases/conditions in women (“acne vulgaris” (acne papulopustulosa, acne nodulocystica); seborrhea; androgenic alopecia; hirsutism).

Contraindications

Diane-35® is contraindicated in the presence of any of the diseases/conditions/risk factors listed below:

• thrombosis (venous and arterial) and thromboembolism (including deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular disorders - currently or in history;
• conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;
• known predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (anticardiolipin antibodies, lupus anticoagulant);
• migraine with a history of focal neurological symptoms;
• diabetes mellitus with vascular complications;
• the presence of a high risk of venous or arterial thrombosis (for example, severe dyslipoproteinemia) (see section "Special instructions");
• uncontrolled arterial hypertension;
• pancreatitis with severe hypertriglyceridemia currently or in history;
• severe liver disease (including excretory system disorders such as Dubin-Johnson and Rotor syndromes) until liver function tests return to normal;
• liver tumors (benign or malignant) currently or in history;
• identified hormone-dependent malignant diseases (including genital organs or breast) or suspicion of them;
• bleeding from the genital tract of unknown etiology;
• smoking at the age of 35 years and older;
• a history of idiopathic jaundice and/or severe itching associated with cholestasis during previous pregnancies; otosclerosis with hearing impairment; herpes;
• sickle cell anemia;
• combined use with other hormonal contraceptives;
• pregnancy or suspicion of it;
• breastfeeding period;
• hypersensitivity to cyproterone and/or ethinyl estradiol, or to any of the excipients of the drug Diane-35®;
• intolerance to lactose, sucrose, lactase deficiency, sucrase/isomaltase, glucose-galactose malabsorption;
• combined use with direct-acting antiviral drugs (DAAs) containing ombitasvir, paritaprevir, dasabuvir or a combination of these substances (see section “Interaction with other drugs”). Diane-35® is not intended for use in men.

If any of these diseases/conditions/risk factors appear for the first time while taking Diane-35®, the drug should be stopped immediately.

Directions for use and doses

Diane-35® should not be used solely for the purpose of contraception. For the purpose of contraception, the drug can be used only in women with androgen-dependent diseases (acne with or without seborrhea; and/or hirsutism).

To achieve a therapeutic effect and provide the necessary contraception, Diane-35® should be taken regularly.

If any hormonal contraceptive drug was used before starting to take Diane-35®, its use should be discontinued.

The dosage regimen of Diane-35® coincides with the dosage regimen of most combined oral contraceptives (COCs). Thus, the rules for taking other COCs apply to taking Diane-35®.

Irregular use of the drug Diane-35® can lead to acyclic bleeding, a decrease in the therapeutic effect and contraceptive effectiveness. When used correctly, the Pearl index (an indicator reflecting the rate of pregnancy in 100 women during a year of using a contraceptive) is approximately 1.

The calendar pack of Diane-35® contains 21 tablets. Diane-35® tablets should be taken orally, one every day for 21 days at approximately the same time, with a small amount of water. Each tablet must be taken on the appropriate day of the week indicated on the package, following the arrows. Taking the tablets from the next pack begins after a 7-day break from taking the tablets, during which bleeding usually occurs (mini-pill, injectable forms, implant) or from a progestogen-releasing intrauterine therapeutic system

You can switch from the mini-pill to Diane-35® on any day (without a break), from an implant or intrauterine contraceptive with progestin - on the day of its removal, from the injection form - on the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion (including spontaneous) in the first trimester of pregnancy

You can start taking the drug immediately. If this condition is met, additional contraception is not required.

After childbirth (in the absence of breastfeeding) or termination of pregnancy (including spontaneous) in the second trimester

It is recommended to start taking the drug 21-28 days after childbirth (in the absence of breastfeeding) or termination of pregnancy in the second trimester. If the drug is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

If sexual contact took place before starting to take Diane-35®, it is necessary to exclude pregnancy or wait until the first menstruation.

Taking missed pills

If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. The woman should take the tablet as soon as possible, and the next tablet should be taken at the usual time.

If the delay in taking the pills is more than 12 hours, contraceptive protection may be reduced. The more pills you miss and the closer the missed pill is to the 7-day break in taking pills, the higher the chance of pregnancy.

In this case, you can be guided by the following two basic rules:

• The drug should never be interrupted for more than 7 days.
• 7 days of continuous tablet use are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian axis.

Accordingly, if the delay in taking pills exceeds 12 hours (the interval from the moment of taking the last pill is more than 36 hours), depending on the week when the pill was missed, you must:

• First week of taking the drug

Take the last missed pill as soon as possible, as soon as the woman remembers (even if this means taking two pills at the same time). The next tablet should be taken at the usual time. Over the next 7 days, an additional barrier method of contraception (for example, a condom) must be used. If sexual intercourse took place within 7 days before missing a pill, the possibility of pregnancy must be taken into account.

• Second week of taking the drug

Take the last missed pill as soon as possible, as soon as the woman remembers (even if this means taking two pills at the same time). The next tablet should be taken at the usual time.

If a woman has taken the pills correctly during the previous 7 days, there is no need to use additional contraceptive measures. Otherwise, or if you miss two or more tablets, you must additionally use barrier methods of contraception (for example, a condom) for the next 7 days.

• Third week of taking the drug

The risk of decreased contraceptive reliability is inevitable due to the upcoming break in taking pills.

In this case, you must adhere to the following algorithms:

• If all tablets have been taken correctly in the 7 days preceding the first missed pill, there is no need to use additional methods of contraception. When taking missed pills, follow steps 1 or 2.
• If during the 7 days preceding the first missed tablet the tablets were taken incorrectly, then during the next 7 days it is necessary to additionally use a barrier method of contraception (for example, a condom) and in this case you should follow point 1 for taking the missed tablets.

1. It is necessary to take the missed pill as soon as possible, as soon as the woman remembers (even if this means taking two pills at the same time). The next tablets are taken at the usual time until the tablets in the current pack are gone. You should start taking the tablets from the next pack immediately without the usual 7-day break. Bleeding, spotting and/or breakthrough bleeding on the days of taking the drug.

2. You can also stop taking pills from the current pack, take a break of 7 days or less (including days you missed pills), and then start taking pills from a new pack.

If a woman misses taking pills, and during the break in taking she does not have bleeding ("Special instructions" and "With caution").

Stopping taking Diane-35®

Taking Diane-35® can be stopped at any time. If a woman is not planning a pregnancy, other methods of contraception should be considered. If you are planning a pregnancy, you should simply stop taking Diane-35® and wait for natural menstrual bleeding.

Additional information for certain patient groups

In teenage girls

The drug Diane-35® is indicated only after the onset of menarche (establishment of the menstrual cycle).

Postmenopausal patients

Not applicable. The drug Diane-35® is not indicated after menopause.

Patients with liver dysfunction

Diane-35® is contraindicated in women with severe liver disease until liver function tests return to normal (see also section “Contraindications”).

Patients with impaired renal function

The drug Diane-35® has not been specifically studied in patients with impaired renal function. Available data do not provide a basis for adjusting the dosage regimen in such patients.

Storage conditions

Store out of the reach of children at a temperature not exceeding 30 °C.

Best before date

5 years. Do not use after the expiration date.

special instructions

Before starting or resuming the use of drugs containing this combination, a woman must undergo a thorough general medical (including measurement of blood pressure, heart rate, determination of BMI) and gynecological examination, including examination of the mammary glands and cytological examination of scrapings from the cervix (Papanicolaou test), and exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least 2 times a year.

The woman should be warned that this combination does not protect against HIV infection and other sexually transmitted diseases.

There is evidence of an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) when using COCs. These diseases are rare. The risk of developing venous thromboembolism is greatest in the first year of taking such drugs. The risk of developing thrombosis (venous and/or arterial) and thromboembolism increases: with age; in smokers (with increasing number of cigarettes or increasing age, the risk further increases, especially in women over 35 years of age) with a family history (for example, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of a hereditary predisposition, the woman should be referred to an appropriate specialist to decide on the possibility of using COCs; for obesity (BMI > 30 kg/m2), dyslipoproteinemia, arterial hypertension, migraine, heart valve disease, atrial fibrillation, prolonged immobilization, major surgery, any surgery on the lower extremities or major trauma. In these situations, it is necessary to stop using the COC (in the case of a planned operation, at least 4 weeks before it) and not to resume taking it for 2 weeks after the end of immobilization.

The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.

The increased risk of thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders may also occur in diabetes mellitus, SLE, tetany, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or UC), and sickle cell anemia.

An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs.

An important risk factor for the development of cervical cancer is the persistence of papillomavirus. Some epidemiological studies suggest an additional increase in this risk with long-term use of COCs, however, this remains controversial because the extent to which the studies account for associated risk factors such as cervical screening and sexual behavior, including less frequent use, is unclear. barrier methods of contraception.

The connection between the use of COCs and breast cancer has not been proven. There is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs. The increased risk gradually disappears within 10 years of stopping these drugs. The observed increased risk may be a consequence of careful monitoring and earlier diagnosis of breast cancer in women using COCs. In women who have ever used COCs, breast cancer is diagnosed at earlier stages and is clinically less severe than in women who have never used COCs.

In isolated cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors was observed, which in some cases led to life-threatening intra-abdominal bleeding. In case of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding, the differential diagnosis should take into account the possibility of a liver tumor in patients taking COCs.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while using COCs.

Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases in blood pressure have rarely been reported. However, if a persistent, clinically significant increase in blood pressure develops during the use of COCs, these drugs should be discontinued and treatment of arterial hypertension should be initiated. Taking COCs can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.

The following conditions have been reported to develop or worsen during both pregnancy and COC use, but their association with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; SLE; hemolytic-uremic syndrome; Sydenham's chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and UC associated with the use of COCs have also been described.

In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COC use.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose COCs (<0.05 mg ethinyl estradiol). However, women with diabetes should be carefully monitored while using COCs.

Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while using COCs.

Treatment (contraception) must be stopped immediately if pregnancy occurs, the development of migraine-like headaches (if they did not exist previously), the appearance of early signs of phlebitis or phlebothrombosis (unusual pain or swelling of the veins in the lower extremities), the appearance of jaundice, visual impairment, cerebrovascular disorders, stabbing pain of unknown etiology when breathing or coughing, pain and a feeling of tightness in the chest, with increased blood pressure.

Admission should also be stopped 3 months before a planned pregnancy, 6 weeks before a planned surgical intervention and during prolonged immobilization.

Taking COCs may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport proteins, carbohydrate metabolism, coagulation and fibrinolysis parameters.

It is possible that the results of skin allergy tests may change and the concentrations of LH and FSH may decrease.

Due to the fact that the contraceptive effect is fully manifested by the 14th day from the start of use, in the first 2 weeks it is recommended to additionally use non-hormonal (barrier) methods of contraception.

Prescription after childbirth is recommended no earlier than the first normal menstruation after childbirth.

In cases of acyclic bleeding during the first 3 weeks of hormonal contraception, it is possible to continue taking the drug; as a rule, the bleeding stops on its own. If there is no bleeding during the 7-day interval between taking the drug, taking the tablets should be stopped until pregnancy is ruled out.

While using COCs, irregular (acyclic) spotting/bleeding from the vagina (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.

Description

Monophasic oral contraceptive with antiandrogenic properties.

Dosage form

Light yellow film-coated tablets, round, biconvex.

Use in children

The drug Diane-35 is indicated only after the onset of menarche (the establishment of the menstrual cycle).

Action

Combined low-dose monophasic contraceptive with antiandrogenic activity. The mechanism of action is due to the antiandrogenic steroidal agent it contains - cyproterone acetate and oral estrogen - ethinyl estradiol. Blocks androgen receptors, inhibits the secretion of gonadotropic hormones by the pituitary gland.

Cyproterone

has the ability to competitively bind to receptors of natural androgens (including testosterone, dihydroepiandrosterone, androstenedione), formed in small quantities in the body of women, mainly in the adrenal glands, ovaries and skin. By blocking androgen receptors in target organs, it reduces the phenomenon of androgenization in women (due to disruption of processes mediated by hormone-receptor complexes at the level of basic intracellular mechanisms). Along with antiandrogenic properties, it has gestagenic activity that imitates the properties of the corpus luteum hormone. Inhibits the secretion of gonadotropic hormones by the pituitary gland and inhibits ovulation, which determines its contraceptive effect.

Ethinyl estradiol

enhances the central and peripheral effects of cyproterone on ovulation, maintains the high viscosity of cervical mucus, which makes it difficult for sperm to penetrate into the uterine cavity and helps ensure a reliable contraceptive effect.

Side effects

Determination of the frequency of adverse reactions: often (>1/100 and <1/10); uncommon (>1/1000 and <1/100); rare (>1/10,000 and <1/1000).

From the nervous system: often - headache, depression, mood swings; infrequently - migraine, decreased libido; rarely - increased libido.

From the digestive system: often - nausea, abdominal pain; infrequently - vomiting, diarrhea.

From the reproductive system and mammary gland: often - pain in the mammary glands, engorgement of the mammary glands; infrequently - hypertrophy of the mammary glands; rarely - intermenstrual bleeding, oligomenorrhea.

Other: often - weight gain; uncommon - fluid retention in the body, rash, urticaria; rarely - allergic reactions, erythema nodosum, erythema multiforme, weight loss, deterioration of tolerance to contact lenses, with long-term use - chloasma.

All women taking combined oral contraceptives (COCs) are at increased risk of thrombosis and thromboembolism, and a slight increase in the risk of occurrence and worsening of other diseases. When taking COCs, irregular (acyclic) vaginal bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use.

Use during pregnancy and breastfeeding

Use is contraindicated during pregnancy and lactation.

Interaction

The effect on hepatic metabolism of drugs that induce liver microsomal enzymes can lead to an increase in the clearance of sex hormones, which in turn can lead to breakthrough bleeding or reduced contraceptive reliability. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort.

HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and combinations thereof also have the potential to affect hepatic metabolism.

During the use of drugs that affect liver microsomal enzymes, and for 28 days after their discontinuation, a barrier method of contraception should be additionally used.

Some antibiotics (eg, penicillins and tetracyclines) may reduce the enterohepatic circulation of estrogens, thereby lowering ethinyl estradiol concentrations. During the use of antibiotics (such as penicillins and tetracyclines) and for 7 days after their discontinuation, a barrier method of contraception should be additionally used.

COCs may affect the metabolism of other drugs, resulting in increased (eg cyclosporine) or decreased (eg lamotrigine) plasma and tissue concentrations. Adjustment of the drug dosage regimen may be required.

Overdose

No serious adverse events have been reported following overdose.
Symptoms that may occur in case of overdose: nausea, vomiting and withdrawal bleeding. The latter can occur in girls who have not reached the age of menarche when taking the drug through negligence. There is no specific antidote; symptomatic treatment should be carried out.

Impact on the ability to drive vehicles and operate machinery

Not found.

Interaction

A number of medications may reduce the effectiveness of this contraceptive. These are drugs for the treatment of epilepsy ( phenytoin , primidone , barbiturates ), tuberculosis ( Rifampicin ), a number of antibiotics ( tetracyclines , Ampicillin , Griseofulvin ).

Before starting to take Diane-35, a woman must inform her doctor about all the drugs she is taking.

special instructions

If any of the risk factors are present, before starting to take the drug, you must carefully determine the likely risk and expected benefit. There is evidence of an increase in the incidence of thrombosis and thromboembolism when using oral contraceptives. The severity and frequency of migraines are likely to increase when using this method of contraception. There is evidence of a possible increase in the likelihood of developing cervical cancer, but this connection has not been clearly proven.

Women who are prone to developing chloasma should not spend long periods of time in the sun while taking oral contraceptives.

Women with diabetes need constant supervision by a specialist during the period of use of Diane-35.

It should be borne in mind that the use of Diane-35 may affect the results of laboratory tests.

In the first months of use, menstrual bleeding may be irregular. Sometimes during a break in taking pills there may be no withdrawal bleeding.

With prolonged use of the Diane-35 contraceptive, a woman should be examined by a gynecologist every 6 months.

It should be borne in mind that pregnancy can occur almost immediately after discontinuation of the drug. If a woman suspects that she became pregnant while discontinuing a contraceptive, she needs to consult a specialist.

Does not affect the ability to drive.

Special instructions for the use of the drug Diane-35

Clinical data regarding estrogen/progestogen combinations, such as Diane-35, are based on experience with the use of COCs. With this in mind, the following warnings regarding taking COCs also apply to this drug. If any of the following conditions/risk factors are present, it is necessary to evaluate the benefits of using Diane-35 and the possible risks, taking into account the individual characteristics of each patient and discuss this with her before she decides to take the drug. If any of the following conditions or risk factors become worse, worse, or occur for the first time, it is recommended that you consult your doctor. The doctor must decide whether to stop using Diane-35. Circulatory disorders Based on the results of epidemiological studies, there is an association between the use of COCs and an increased risk of venous and arterial thrombotic and thromboembolic diseases, such as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. These conditions occur rarely. Venous thromboembolism (VTE), manifested as venous thrombosis and/or pulmonary embolism, can occur with the use of any COC. The risk of venous thromboembolism is highest during the 1st year of COC use. The incidence of VTE in patients taking oral contraceptives with low doses of estrogens (≤0.05 mg ethinyl estradiol) is up to 4 cases per 10,000 women/year compared with 0.5–3 cases per 10,000 women/year in women not using oral contraceptives. The incidence of VTE associated with pregnancy is 6 cases per 10,000 women/year. Thrombosis of other blood vessels, such as arteries and veins of the liver, kidneys, mesenteric vessels, cerebral vessels or retina, has been extremely rarely reported in women using COCs. There is no consensus regarding the connection between these complications and the use of PDAs. Symptoms of venous or arterial thrombotic/thromboembolic events or stroke may include: unilateral lower extremity pain or swelling; sudden severe chest pain radiating to the left arm; sudden shortness of breath; sudden onset of cough; any unusual, severe, prolonged headache; sudden decrease or complete loss of vision; diplopia; speech impairment or aphasia; vertigo; collapse with or without partial epileptic seizure; weakness or very severe sudden numbness of one side or one part of the body; motor impairment; symptoms of acute abdomen. Factors that increase the risk of venous or arterial thrombotic/thromboembolic events or stroke:

• age;
• tobacco smoking (in combination with heavy smoking and with age, the risk increases, especially in women over 35 years of age);
• family history (for example, cases of venous or arterial thromboembolism in siblings or parents at a relatively early age). If a hereditary predisposition is suspected, before a decision is made on the use of any COC, the patient should be referred for consultation to an appropriate specialist;
• obesity (body mass index - more than 30 kg/m2);
• dyslipoproteinemia;
• AH (arterial hypertension);
• migraine;
• heart valve pathology;
• atrial fibrillation;
• prolonged immobilization, radical surgical interventions, any surgical operations on the lower extremities, significant injuries. In these cases, it is recommended to stop using the COC (for planned operations at least 4 weeks before they are performed) and not restore it earlier than 2 weeks after complete remobilization.

There is no consensus regarding the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism. It is necessary to take into account the increased risk of thromboembolism in the postpartum period. Other diseases that may be associated with serious circulatory disorders include: diabetes mellitus; systemic lupus erythematosus; hemolytic uremic syndrome; chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia. An increased incidence of migraine or its exacerbation during the period of use of COCs (which may be a harbinger of cerebrovascular accident) requires urgent cessation of COC use. Biochemical indicators characteristic of hereditary or acquired susceptibility to venous or arterial thrombosis include: activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies). When analyzing the risk/benefit ratio, the doctor must take into account that adequate treatment for the conditions mentioned above can reduce the associated risk of thrombosis, and also that the risk of thrombosis associated with pregnancy is higher than with the use of COCs in low doses (≤0.05 mg ethinyl estradiol). Tumors The most important risk factor for the development of cervical cancer is the persistence of papillomavirus. Some epidemiological studies suggest an additional increase in this risk with long-term use of COCs, however, this statement is controversial because the extent to which the study results take into account concomitant risk factors, such as cervical smears and sexual behavior, including the use of barrier methods of contraception, is unclear. . The results of a meta-analysis based on data obtained from 54 epidemiological studies indicate a slight increase in the relative risk (RR = 1.24) of developing breast cancer in women using COCs. This increased risk gradually disappears within 10 years of stopping taking COCs. Because breast cancer is rarely diagnosed in women under 40 years of age, the increase in breast cancer diagnosis among current or recent COC users is small relative to the overall risk of breast cancer. The results of these studies do not provide evidence of a causal relationship. The increased risk may be due to both earlier diagnosis of breast cancer in women using COCs, the biological effects of COCs, or a combination of both factors. There is a tendency that breast cancer detected in women who have ever taken COCs is clinically less severe than in those who have never taken COCs. In isolated cases, benign, and even less often, malignant liver tumors were noted in women using COCs, which sometimes led to life-threatening intra-abdominal bleeding. If there are complaints of severe pain in the epigastric region, liver enlargement or signs of intra-abdominal bleeding, the differential diagnosis should take into account the possibility of a liver tumor in women taking COCs. Other conditions Women with hypertriglyceridemia or a family history of this disorder are at risk of developing pancreatitis when using COCs. Although slight increases in blood pressure have been reported in many women taking COCs, clinically significant increases in blood pressure are rare. However, if prolonged clinically significant hypertension (arterial hypertension) occurs while taking a COC, then it is sometimes advisable to discontinue the COC and direct treatment to the hypertension (arterial hypertension). The occurrence or exacerbation of the following diseases has been reported during pregnancy and with the use of COCs, but their relationship with the use of COCs has not been conclusively established: jaundice and/or pruritus associated with cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea, herpes of pregnancy, hearing loss associated with otosclerosis. In acute or chronic liver dysfunction, it may be necessary to stop taking COCs until liver function tests return to normal. If cholestatic jaundice relapses, which first occurred during pregnancy or previous use of sex hormones, taking COCs should be discontinued. Although COCs may affect peripheral insulin resistance and glucose tolerance, there are no data regarding the need to change the therapeutic regimen in women with diabetes mellitus taking low-dose COCs (containing ≤0.05 mg ethinyl estradiol). However, women with diabetes should be closely monitored while taking COCs. Crohn's disease and ulcerative colitis may be associated with COC use. Chloasma can sometimes occur, especially in women with a history of chloasma during pregnancy. Women prone to chloasma should avoid exposure to direct sunlight or ultraviolet radiation while taking COCs. Medical examination Before starting or resuming taking Diane-35, a full medical examination should be carried out and the patient’s medical history examined in detail, taking into account contraindications (see CONTRAINDICATIONS) and cautions (see APPLICATION). When using COCs, periodic examinations are recommended, which is very important, since contraindications (for example, transient circulatory disorders, etc.) or risk factors (for example, a family history of venous or arterial thrombosis) may arise for the first time while taking the drug. The frequency and nature of these examinations should be based on existing standards of medical practice, taking into account the individual characteristics of each woman, however, special attention is paid to examination of the pelvic organs, including a standard analysis of cytology of the cervix, abdominal organs, mammary glands, and determination of blood pressure. It is necessary to warn the woman that Diane-35, like other oral contraceptives, does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Reduced effectiveness The effectiveness of Diane-35 may be reduced if a pill is missed, gastrointestinal dysfunction or other medications are used. Cycle control When taking oral contraceptives, intermenstrual bleeding (spotting or breakthrough bleeding) may occur, especially during the first few months of treatment. Taking this into account, examination in the event of any intermenstrual bleeding should be carried out only after a period of adaptation of the body to the drug, which is approximately 3 cycles. If cycle irregularities continue or recur after several normal cycles, non-hormonal causes of bleeding should be considered and appropriate investigations should be carried out to exclude the presence of a tumor or pregnancy. Diagnostic measures can include curettage. Some women may not experience menstrual bleeding during a break from taking the drug. Pregnancy is unlikely when you take COCs as directed. However, if the contraceptive is taken irregularly or if menstrual-like bleeding is absent for 2 cycles, pregnancy must be ruled out before continuing to take the COC. Pregnancy and lactation The drug is contraindicated for use during pregnancy. If pregnancy occurs while using the drug Diane-35, the drug should be discontinued. However, according to the results of embryotoxicity studies when using a combination of two active components of the drug, there was no confirmation of the teratogenic effect of the drug during organogenesis. Although taking cyproterone acetate in high doses during the hormone-sensitive phase of genital differentiation causes the appearance of female sexual characteristics in male fetuses, during the observation of newborn boys whose mothers took cyproterone acetate during pregnancy, no female sexual characteristics were detected. The use of Diane-35 is contraindicated during breastfeeding. Cyproterone acetate passes into breast milk. About 0.25% of the dose of cyproterone acetate taken by the mother enters the child's body with milk, which corresponds to 1 mcg/kg body weight and 0.2% of the daily dose of ethinyl estradiol. Impact on the ability to drive vehicles and operate machinery No impact was noted.

Reviews about Diana-35

Those who have taken these birth control pills leave very different reviews. Many women note that the drug is easy to use and provides a lasting positive effect.

Reviews of Diana-35 for acne are also positive, since after a relatively short period of use, many women got rid of acne on their faces and noted a significant improvement in their skin.

In the discussion of Diana-35, doctors’ reviews are often positive. Reviews from gynecologists indicate that the drug is generally effective. However, there are many complaints online related to negative actions as a consequence of taking this contraceptive. In particular, women write about nausea, weight gain, rapid heartbeat, general decrease in tone, etc.

There are also many reviews indicating that pregnancy occurred after using this drug in cases where women had previously been unable to conceive a child.

Price Diana-35, where to buy

You can buy birth control pills at any pharmacy with a doctor's prescription. The price of Diana-35 in pharmacies is from 1000 rubles. per package.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

Pharmacy Dialogue

• Diane-35 (other No. 21) Bayer
  RUB 1,084 order

show more

Pharmacy24

• Diane-35 No. 21 tablets Promotion 5+1 Bayer Pharma AG, Niemecchina/Bayer Weimar GmbH i Co.
  KG, Nimechchyna 1245 UAH. order

PaniPharmacy

• Diane tablets Diane-35 etc. No. 21 Germany, Bayer Weimar

  273 UAH order

show more